Gareta, Dickman Pangaume2014-02-062014-02-062013http://hdl.handle.net10539/13683A research report submitted to, the Faculty of Health Sciences, University of Witwatersrand, in partial fulfilment of the requirements for the degree of Master of Science in Population based field epidemiology March, 2013Introduction: Access to highly active antiretroviral therapy has dramatically increased worldwide since 2004. However, the emergence of HIV drug resistance presents huge obstacle in ART scale up as it contributes to treatment failure and poses a greater risk of disease progression and loss of treatment options. The study therefore investigated the risk factors and the association of HIV drug resistance, virological failure and CD4 cell count changes in patients on ART at Aurum Institute for Health Research in South Africa. Methods: A cohort of HIV infected patients who developed virological failure of their first HAART regimen was assessed. A genotypic resistance testing was performed using stored plasma on a subset of patients at first detection of virological failure. Data were collected prospectively on all registered patients using standardised forms. Clinical data was obtained from laboratory and pharmacy electronic records. Logistic regression and Cox proportional hazard models were used to assess factors associated with HIV drug resistance and virological failure respectively. Linear mixed-effects regression models were used to assess the changes in the CD4 cell count among patients who developed HIVDR. Results: Between January 2003 and December 2010, a total of 146 ART-treated patients who experienced virological failure were assessed. Of these, 108 (74%) developed HIVDR, of whom 80 (74%) were males; the median CD4 cell count at ART initiation was 121 cells/mm3 (interquartile range, 61-210). The most frequent NNRTI mutations patterns found were mutations leading to resistance to NNRTI agents with 33% having NNRTI resistance. The second most common resistance v pattern was resistance to lamivudine conferred by the M184V mutation (30%). The multivariable analysis showed that higher CD4 cell count at HIVDR detection was significantly associated with the reduced odds of developing HIV drug resistant mutation after adjusting for gender and age(adjusted OR=0.37, 95% CI 0.15–0.94). Similarly, there was significant association between age at ART initiation (adjusted HR=0.71, 95% CI 0.52–0.97) and CD4 cell count during follow-up (adjusted HR= 0.54 95% CI 0.36–0.81) with virological failure in those patients who developed HIVDR. The CD4 cell count slope on average increased by 10 cells per mL per year for the patients without any resistance (average annual change 9.89 cells per mL, 95% CI -6.90-26.69) and decreased by 10 cells per mL per year for patients who had any resistance (average annual change -9.61 cells per mL, 95% CI -19.41- 0.17). Conclusion and recommendation: HIV drug resistant virus was found in 74% of the South African patients who were accessing HIV care at Aurum Heath Institute and developed virological failure of first HAART regimen. Higher CD4 count at detection of HIVDR was significantly associated with lower risk of developing HIV drug resistant virus. Lower CD4 count and male gender were significantly associated with the development of virological failure. Patients with virological failure had significantly great CD4 count declines when any mutation and thymidine analog mutation (TAM) mutation were present. There is a great need therefore for multifaceted approach to target interventions that aim to increase patients CD4 cell counts. Patients should be either screened, possibly with HIVDR testing, prior to reinitiation of a first-line regimenenAntiretroiviral Therapy, Highly ActiveDrug ResistanceThesis